In a placebo-controlled, proof-of-concept study, LX4211 provided clinically meaningful and statistically significant reductions (p<0.05) in post-prandial glucose in diabetes patients with moderate to severe renal impairment (Stage 3 and 4 kidney disease). Importantly, these effects were maintained in a sub-group with the most advanced renal impairment, pre-defined as those with glomerular filtration rate (GFR) less than 45 ml/min/1.73 m 2. LX4211 also produced significant elevations in GLP-1, a hormone involved in control of glucose and appetite.

Renal impairment occurs in approximately 30% of patients with type 2 diabetes and represents a major unmet medical need with limited treatment options. LX4211's inhibition of SGLT1 in the gastrointestinal (GI) tract, reducing glucose absorption and triggering GLP-1 secretion, offers the potential for treating this medically challenging population with compromised kidney function. In previous Phase 2 studies, LX4211 improved glycemic control in patients with type 2 diabetes with normal renal function.

"Our hypothesis was that LX4211 would improve glycemic control even in patients with the greatest degree of renal impairment due to its inhibition of SGLT1 in the GI tract," said Pablo Lapuerta, M.D., Lexicon's chief medical officer. "The post-prandial glucose reductions and GLP-1 elevations observed in this study population support the rationale for demonstrating effective HbA1c reduction in a larger, longer-term Phase 3 trial, and provide further support for the clinical differentiation of LX4211 as a first-in-class dual SGLT1 and SGLT2 inhibitor."

In this multicenter study, 30 patients with poorly controlled type 2 diabetes and moderate to severe renal impairment were randomized to either placebo or a 400 mg dose of investigational drug LX4211 taken orally once per day before breakfast. Patients' post-prandial glucose was measured after a standardized meal both at baseline before treatment and after one week of therapy. In addition to achieving the primary efficacy objective of post-prandial glucose reduction, there were no serious adverse events observed in the study and no discontinuations of LX4211 due to adverse events. Lexicon plans to present full results of the study at scientific congresses in 2014.